Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001058147 | SCV001222694 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 579 of the MEN1 protein (p.Leu579Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 853356). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002402420 | SCV002710199 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | The p.L579F variant (also known as c.1735C>T), located in coding exon 9 of the MEN1 gene, results from a C to T substitution at nucleotide position 1735. The leucine at codon 579 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV001058147 | SCV004194460 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-08-08 | criteria provided, single submitter | clinical testing |